Abstract

The primary objective was to determine if multi-omic molecular profiling (MMP) informed selection of approved cancer treatments could change the clinical course of disease for patients with previously treated metastatic breast cancer (MBC) (i.e., produce a growth modulation index (GMI) ≥1.3). GMI was calculated as the ratio of progression free survival on MMP-selected therapy/time to progression on last prior treatment. To meet the primary objective at least 35 % of the subjects should demonstrate a GMI ≥1.3. Secondary endpoints included determining the response rate (according to RECIST 1.1), the percent of patients with non-progression at 4 months, and overall survival in patients whose therapy is selected by molecular profiling and proteomic analysis. Eligible patients had MBC, with ≥3 prior lines of therapy. A multi-omic based approach was performed incorporating multiplexed immunohistochemistry, c-DNA microarray, and phosphoprotein pathway activation mapping by reverse phase protein array. MMP was performed on fresh core biopsies; results were generated and sent to a Treatment Selection Committee (TSC) for review and treatment selection. Three sites enrolled 28 patients, of which 25 were evaluable. The median range of prior treatment was 7 (range 3–12). The MMP analysis and treatment recommendation were delivered within a median of 15.5 days from biopsy (range 12–23). The TSC selected MMP-rationalized treatment in 100 % (25/25) of cases. None of the MMP-based therapies were the same as what the clinician would have selected if the MMP had not been performed. GMI ≥1.3 was reported in 11/25 (44 %) patients. Partial responses were noted in 5/25 (20 %), stable disease in 8/25 (32 %) and 9/25 (36 %) had no progression at 4 months. This pilot study demonstrates the feasibility of finding possible treatments for patients with previously treated MBC using a multiplexed MMP-rationalized treatment recommendation. This MMP approach merits further investigation.

Notes

Acknowledgments

The authors thank the patients and their families who participated in this clinical trial and the Side-Out Foundation. The Side-Out Foundation sponsored and provided the funding for the study. Side-Out Foundation and TD2 were responsible for the study design. TD2 coordinated the collection, monitoring, management, interpretation, and analysis of the data. The corresponding author (GSJ) had full access to all the data in the study and final responsibility for the decision to submit for publication. This trial is registered with ClinicalTrials.gov, number NCT01074814.

Conflict of interests

Gayle Jameson reports grants from Side-Out Foundation and serves in a Consultant/Advisory role with Celgene. Dr. Petricoin reports grants from Side-Out Foundation, during the conduct of the study; University, personal fees from Perthera, Inc., outside the submitted work; In addition, Dr. Petricoin has a patent Methods for the Isolation and Analysis of Cellular Protein Content 6,969,614 with royalties paid, and a patent mTOR pathway Theranostic US8628931 B2 pending and Stock ownership: Theranostics Health, Inc. and Pethera, Inc. Dr. Sachdev reports grants from Celgene, grants from Pfizer, drug support from Genentech and advisory board payment from Celgene outside the submitted work. Dr. Liotta reports personal fees from Theranostics Health, Inc., outside the submitted work; and stock ownership: Theranostics Health. NIH royalty fees received for Analysis of Cellular Protein Content6,969,614, and Laser Capture Microdissection 5,843,644; 5,843,657;6,010,888; 6,204,0030; 6,251,516. Dr. Loesch reports personal fees from Caris Life Sciences, during the conduct of the study. Dr. Anthony reports personal fees from Caris Life Sciences, during the conduct of the study. Dr. Chadha declares that she has no conflict of interest. Dr. Wulfkuhle reports Stock Ownership: Theranostics Health. Rosa Gallagher reports grants from Side Out Foundation, during the conduct of the study. Kimberley Reeder reports grants from Side-Out Foundation, during the conduct of the study. Dr. Pierobon reports grants from Side-Out Foundation, during the conduct of the study; Stock Ownership: Theranostics Health, serves in a Consultant/Advisory role with Perthera. Monica Fulk declares that she has no conflict of interest. Nina Cantafio reports personal fees from Translational Drug Development LLC (TD2), during the conduct of the study; and previous contract work with Caris Life Sciences. Brian Dunetz reports Employment Position- Chief Operating Officer Side Out Foundation, uncompensated. Dr. Mikrut reports personal fees from Translational Drug Development LLC (TD2), during the conduct of the study. Dr. Von Hoff reports personal fees from Caris Life Sciences, as Director of Clinical Research during the conduct of the study and Stock Ownership: Caris Life Sciences. Dr. Robert reports grants from Side-Out Foundation, during the conduct of the study.